BioFormer: Rethinking Cross-Subject Generalization via Spectral Structural Alignment in Biomedical Time-Series

Clinical time-series learning is routinely constrained by small, heterogeneous cohorts and protocol drift, while its downstream use spans both classification (e.g., pathology diagnosis) and regression (e.g., temporal forecasting). These constraints make foundation-model pretraining appealing, but raises an important question of which inductive biases should the pretraining objective impose so that representations transfer across task types and subjects. We study this question in pathological gait analysis for spinal cord injury (SCI) via PathoFM, an encoder-centric transformer pretrained on multivariate gait windows with three complementary objectives: Local Completion (reconstruct contiguous masked spans to enforce local structure), Temporal Continuity (predict a masked mid-horizon continuation from an observed prefix to enforce smoothness and causal consistency), and Unsupervised In-Context Dynamics (support-query reconstruction conditioned on subject exemplar windows via attention). Empirically comparing objective families (grouping/contrastive, dynamics-based, and generative reconstruction), we find that dynamics-centric mixtures produce the most balanced transfer: grouping objectives favor discriminative margins but can degrade magnitude fidelity needed for continuous targets, whereas reconstruction-only objectives preserve waveform structure but may underperform on classification. Overall, combining local reconstruction with temporal continuity, and adding in-context conditioning when exemplar access is realistic, yields robust subject-generalizing representations.

Deep learning for cross-subject EEG decoding is hindered by high inter-subject variability, which introduces a severe domain shift between training and unseen test subjects. This survey presents a comprehensive review of deep learning methodologies specifically engineered to address this cross-subject generalization challenge. To ground this analysis, we formalize the cross-subject setting as a multi-source domain problem and delineate the rigorous, subject-independent evaluation protocols required for valid assessment. Central to this survey is a systematic taxonomy of the current literature into discrete methodological families, including feature alignment, adversarial learning, feature disentanglement, and contrastive learning. We conclude by examining three critical elements for advancing robust, real-world decoding: the theoretical limitations of current methodologies, the structural value of subject identity, and the emergence of EEG foundation models.

The development of generalizable electroencephalography (EEG) decoding models is essential for robust brain-computer interfaces (BCI) and objective neural biomarkers in mental health. Conventional approaches have been hindered by poor cross-subject and cross-task generalization, owing to high inter-subject variability and non-stationary neural signals. We address this challenge with a zero-shot cross-subject decoding framework on the large-scale Healthy Brain Network dataset, benchmarking a convolutional neural network baseline, a hybrid LSTM, and a Transformer-based foundation model. To adapt the Transformer for regression while averting catastrophic forgetting, we propose a novel progressive unfreezing strategy. The baseline yielded an nRMSE of 0.9991, whereas our fine-tuned Transformer achieved 0.9799 on unseen subjects. This work advances scalable, calibration-free EEG decoding for computational psychiatry and behavioral prediction.